Mucosal secretions, phagocytes, and other components of the nonspecific (innate) host defense system initiate the response to microbial penetration before time-consuming adaptive immunity starts. Survival of plants and invertebrates, which lack adaptive immunity, illustrates effectiveness of host defense based on such innate mechanisms.
Endogenous antimicrobial peptides are significant in epithelia, the barrier to environmental challenge that provides the first line of defense against pathogens. Production of natural antimicrobial peptides by phagocytes has been recognized for a long time. These natural antimicrobial peptides generally have a broad spectrum of activity against bacteria, fungi, and viruses. Martin, E., Ganz, T., Lehrer, R. I., Defensins and Other Endogenous Peptide Antibiotics of Vertebrates, J. Leukoc. Biol. 58, 128-136 (1995); Ganz, T., Weiss, J., Antimicrobial Peptides of Phagocytes and Epithelia, Sem. Hematol. 34, 343-354 (1997).
The search for antimicrobial peptides, however, has been painfully difficult and slow. A rare and difficult find has been bactericidal/permeability-increasing protein (“BPI”), which has been used successfully to treat children with severe meningococcal sepsis. Giroir, B. P., Quint, P. A., Barton, P., Kirsh, E. A., Kitchen, L., Goldstein, B., Nelson, B. J., Wedel, N. I., Carrol, S. F., Scannon, P. J., Preliminary Evaluation of Recombinant Amino-terminal Fragment of Human Bactericidal/Permeability-increasing Protein in Children with Severe Meningococcal Sepsis, Lancet 350,1439-1443 (1997).
It would be an important advance in the science to identify the most active amino acid sequences responsible for broad spectrum antimicrobial activity, which would also be useful in new prophylactic and therapeutic antimicrobial treatments.